Process for producing an arsenobenzene and the product thereof



Patented Sept. 8, 1931 UNITED STATE PATENT OFFICE AUGUST ALBERT, OF" MUNICH, GERMANY, ASSIGNOR TO WINIH'ROP CHEMICAL COMPANY, OFNEW YORK, N. Y., A CORPORATION OF" NLW' YORK PROCESS FOR PRODUCING AN ARS ENOBENZENE' AND THE PRODUCT THEREOF No; Drawing.- Application filed September 24,1926,- Serial No. 137,625, and in Germany'- October 3, 1925.

My resent invention relates to crystallized arseno enzenes. and to a process for producing, the same.

Hitherto arsenobenzenes could only'be obtained in an amorphous, but not in acrystal lized form which alone warrants always a uniform quality and absolute purity of the products.

Only in twoiexceptionalicases and then only with. arsenobenzenes containing unsubstituted hydrocarbon residues (comp. Bertheim, Handbuch der organischen Arsenverbingun-- gen, page 137), one has succeeded in obtaining arsenobenzenes in a crystalline form... Now it is only the substituted: arsenic compounds. which are of. therapeutical interest, these. compounds are, however, impure owing to their amorphous character. It may be easily understood that the degree in which they are tolerable to the human body, the solubility and stability of the said products must vary within rather wide limits. Now the fact that by my new process it is possible to bring sucharsenobenzenes into a crystallized form must be regarded as a considerable technical.-

and. therapeutical advance in. the. art- According to my present invention crystallized arseno-benzenes are obtainable by causing compounds of the general formula:

wherein X represents hydrogen or an alkyl group, Y representsoxygen or the group N.NH.CO.NH A represents As=O or on o=As and the benzene nucleus may be substituted. tube-acted uponwby hy-pophosp'horous acid 111 thepresence of a suitable dissolving or surpend'ing agent. Instead of the hypophosphorous acid one'may usea-salt thereof which acts as an equivalent. In the latter case an additionof a mineral acidsometimes is ad vantageous. Furthermore, I wish it to be understoodthat one-may use as. starting materials'inst-ead of the compoundsof the above given general formula the corresponding compounds of thearsenic oxide type, i. e.,

wherein X represents hydrogen or an alkyl group, Y' representsoxygen or the group:

andthe' benzene nucleus may be substituted. The following examples serve toillustrate my invention, but'are not intended-to limit it thereto. y r 1. 0.3- grams of metashydroxybenzald'ehydearsinic aeid semicarbazone are suspended.

in about 6 cc; of'al'cohol and-dissolved, while heating, with 1,8200. of about- G-NL alcoholic hydrochloric acid. To this alcoholic solution ofthe chloride, when cooled down, there are added about 1,800. of hypophosphorousacid of 25% strength and afterwards about 0,02cc: ofhydriodic acid of specific gravity 1,7. After some time there will separate from the clear, if desired filtered, solution yellow-colored, elongated needles which are frequently pointed and sometimes aggregated in druses. When the crystallization ceases, the arsenobenzene is filtered off by suction and dried in a vacuum. It is soluble in caustic soda to a clear yellow solution. It corre' sponds probably to the formula:

Instead of starting from the arsinic acid, there may first be prepared its chloride, the latter dissolved in alcohol and further reduced as above described.

2. To a solution of 3 grams of dry ammonium hypophosphite in about 42 cc, of dry glacial acetic acid are added 2,1 grams of dry meta-hydroXy-acetophenonearsinic acidsemicarbazone. After the mass has been boiled for about 2 minutes on the reflux-condenser, a clear solution results. The solution is kept boiling for another 15 minutes and then put for 1% hours on the boiling waterbath. The clear solution may, if desired, be freed, while it is still hot, from any traces of impurities by centrifugation or filtration. From the resulting clear intensely brownishyellow solution the arsenobenzene, on standing for a considerable time, separates in the form of beautiful elongated very fine rectangular tablets. In order to accelerate the crystallization-process and to maintain the product quantitatively, there are carefully added by drops immediately on the completion of the reaction 5 cc. of water while slightly shaking, whereupon the crystalline separation soon sets in. In order to obtain the arsenobenzene in a quantitative yield it is further advantageous to allow the mass to stand for a prolonged time, whereupon it is filtered oil by suction and dried in a vacuum. The product gives a clear solution in canstic soda and decomposes above 200 C. according to the manner in which it is heated.

3. A clear solution of 0,53 grams of paraacetophenone-arsineoxide in 10 cc. of hot glacial acetic acid, after being filtered hot, is mixed with a warm solution of about one gram of sodium hypophosphate in 10 cc. of glacial acetic acid and then carefully heated to boiling on the reflux-condenser while continually slightly shaking. The solution, which is at firstv clear, begins to become turbid and gradually separates the arseno-benzene in a crystalline form. The product of the reaction, after being boiled for about 15 minutes on an open flame, is brought on a boiling water-bath, and in some cases it is only then that the crystalline separation sets in. After having heated the mass for about one hour the product is allowed to cool, filtered ofi and dried in a vacuum. The product crystallizes in beautiful light-yellow colored tablets, which are often pointed on both sides and decompose at about 245 C. according to the manner of heating.

4:. One gram of meta-hydroxy-acetophenonearsinic acid-semicarbazone is dissolved hot with about 20 cc. of alcohol and 5 cc. of about 6-N. alcoholic hydrochloric acid and, if required, filtered. After cooling, the solution is mixed with about 5' cc. of aqueous hypophosphorous acid of 25% strength and about 0,06 cc. of hydriodic acid. The clear faint yellow solution separates after some time an arsenobenzene product in crystalline form, which constitutes the meta-hydroxypara-ac'etophenone arsenobenzene, since, by the action of the strong acid it has split off the semicarbazone residue. This arsenobenzene shows the form of pointed needles.

In the following claims the term diluting agent is intended to comprise such solvents as are able to dissolve the starting materials to such an extent that the reduction process may be effected, for instance the lower alcohols of the aliphatic series and glacial acetic acid.

I claim:

1. The process for preparing crystallized arseno benzenes which comprises treating a compound of the general formula:

wherein X represents hydrogen or an alkyl group, Y represents oxygen or the group =N.NH.CO.NH A represents -As=O or and the benzene nuclei may be substituted, with hypophosphorous acid in the presence of a diluting agent.

2. The process for preparing crystallized ar-seno benzenes which comprises treating a compound of the general formula:

wherein X represents hydrogen or an alkyl group, Y represents oxygen or the group =N.NH.CO.NH A represents As=O or OH O-AS VOHY and Z represents hydrogen or a hydroxyl group, with hypophosphorous acid in the presence of a diluting agent.

3. The process for preparing crystallized arseno benzenes which comprises treating a compound of the general formula:

wherein X represents hydrogen or an alkyl group andY represents oxygen or the group =N.NH.CO.NH with hypophosphorous acid in the presence of a diluting agent.

4. The process for preparing crystallized arseno benzenes which consists in suspending 0.3 parts by weight of meta-hydroxy-benzaldehyde-arsenic acid-semicarbazone in about 6 parts by volume of alcohol, dissolving while heating with 1.8 parts by volume of about 6-N. alcoholic hydrochloric acid solution, cooling and filtering the solution thus obtained, adding about 1.8 parts by volume hypophosphorous acid of 25% strength and about 0.02 parts by volume of hydriodic acid of specific gravity 1.7 and keeping the solution in that state for several hours until crystallization is effected.

5. As new products, arseno benzenes corresponding to the general formula:

wherein X represents hydrogen or an alkyl group, Y represents oxygen or the group :=N.NH.CO.NH and the benzene nuclei may be substituted, being crystallized, yellow colored and substantially pure prodnets.

6. As new products, arseno benzenes corresponding to the general formula:

7. As new products, arseno benzenes corresponding to the probable formula:

| QOHQOH S=== S no no.

As As being a crystallized, yellow colored and substantially pure product.

In testimony whereof, I afiix my signature;

AUGUST ALBERT.

wherein X represents hydrogen or an I 

